Animal models have established that dopaminergic (DA) neurons play a role in novelty detection, but pathways driving their activity remain unknown. An influential model suggests that the hippocampus drives dopamine release when novel sensory information is particularly salient. .

     In established task paradigms, novel stimuli evoke a hippocampally-mediated electroencephalographic deflection after 300 ms (novelty P300), but concurrent DA neuron electrophysiology has not been studied in humans

     Eight patients with Parkinson’s disease undergoing deep brain stimulation of the subthalamic nucleus were enrolled.

     The clinical plan included microelectrode recordings of surrounding structures and awake testing, providing an opportunity to record the substantia nigra while the patient participated in an auditory task known to elicit the novelty P300. The task included a frequent standard tone, infrequent target tone, and infrequent novel sounds. Recorded spikes were sorted into clusters representing single neurons. Firing rates of neurons with dopaminergic characteristics were compared across trials by stimulus type after correcting for pre-stimulus baseline.

     31 DA neurons were recorded, and their activity was significantly higher in the period 200-400 ms following novel sounds compared to standard and target tones (p<.001 and p=.009). The peak of this increased activity occurred at approximately 300 ms.

     This is a retrospective study.

     Midbrain DA neuron activity increased concurrently with the onset of the novelty P300, buttressing the hypothesized role of the hippocampus as a regulator of midbrain dopamine release.

     This adds weight to recent proposals for inhibitory stimulation of the hippocampus as a therapeutic strategy for disorders such as schizophrenia.